Karen Bulaklak/Sandbox1 Glucosamine 6 Phosphate Synthase

Discussion


A 3-dimensional model of Glucosamine-6-phosphate synthase was created highlighting vital features of the protein’s isomerase domain:


 * The UDP-GlcNAc binding pocket includes the sidechains Gly474, Val476, Ser484, Thr487, His492 and residues 489-491.
 * Coordinates with metal cation when substrate is bound, possibly indicating that a positive charge is needed to increase the stability of the enzyme-substrate complex.
 * Fructose-6-phosphate interacts with sidechains of Glu591, Lys588, His607. These residues form a small binding domain for F6P, which has yet to be completely characterized.
 * These two important binding sites appear on opposite sides of each chain, perhaps indicating that the substrates do not greatly effect each others’ interaction with the protein.
 * Tetramerization sites create a horizontal line of symmetry across the protein, separating identical subunits (A and D, B and C), a so-called “dimer of dimers.”
 * Beta sheets could also provide internal support to the protein.

A physical model of the isomerase domain, the main ligand binding structure of the protein, can aid in the understanding of its multiple substrate interactions and necessary conformations for enzymatic activity. With this new tool, we can propose ways to inhibit substrate binding, and consequently, the metabolic pathway of C. Albicans.